Objectives/Hypothesis Ostiomeatal complex (OMC) occlusion may play a role in the pathogenesis of some chronic rhinosinusitis (CRS) subgroups, but its role in diffuse mucosal inflammation is strongly debated. The association between radiological OMC occlusion and its draining sinuses in patients with eosinophilic rhinosinusitis (ECRS) compared to non-ECRS is investigated. Study Design Case-control study. Methods Patients with CRS who underwent endoscopic sinus surgery were investigated. Preoperative computed tomography scans were evaluated. Structured histopathology reporting was performed. The study group was patients with high tissue eosinophil >10/high power fields (HPF), and the control group was patients with low tissue eosinophil ≤10/HPF. The radiological relationship of OMC occlusion to the draining sinuses was analyzed in each group. Results Seventy patients with a mean age of 49.7 ± 14.1 years were analyzed. Forty-one (58.6%) patients had high tissue eosinophil >10/HPF. All patients with ECRS had maxillary disease, and there were 36.2% without OMC occlusion. There was no association of OMC occlusion to either the anterior ethmoid (ECRS: odds ratio [OR], 1.84; 95% confidence interval [CI], 0.24-14.14; P =.55; non-ECRS: OR, 1.57; 95% CI, 0.34-7.33; P =.56) or frontal sinuses (ECRS: OR, 0.67; 95% CI, 0.12-3.82; P =.65; non-ECRS: OR, 1.58; 95% CI, 0.45-5.54; P =.47). For patients with non-ECRS, maxillary sinus diseases was present in 96.2% of those with OMC occlusion and 50% of those without (OR, 25.0; 95% CI, 2.77-226.08; P <.001). Conclusions OMC occlusion is not associated with draining sinuses for patients with ECRS. Simple surgical interventions directed at the OMC are unlikely to be of benefit to this CRS subgroup.